1. Technical Field
The present invention relates to a method for treating a subject having a condition involving apoptosis. The present invention also relates to a method for inhibiting enhanced apoptosis.
2. Art Related
Apoptosis is a kind of genetically programmed cell death. Morphologically, apoptosis occurs along with the process as follows: condensation of the nucleus of the cell; cell shrinkage; cytoplasmic vacuolation and cell surface smoothing; enlargement of intercellular space; release of the cell from the pericellular region; fragmentation of the cell (to provide apoptosis body) and phagocytosis of the fragment by macrophage or the like. Biochemically, nucleosomal DNA is cleaved by endonuclease activity into 180-220 bp DNA fragments (Immunology Today 7: 115-119, 1986; Science 245:301-305, 1989, the cited references are herein incorporated by reference).
It has been revealed that apoptosis plays a role not only in physiological cell death concerning generation/differentiation and turnover of normal tissues and cells, but also in some diseases or conditions such as ischemic nerve cell death after cerebral infarction, cell death due to nuclear radiation or anti-cancer agent, cell death due to a toxin or virus infection, lymphocytopenia due to virus infection such as AIDS, photoreceptor cell death in light induced retinal photic injury, autoimmune disease, Alzheimer disease and inflammatory disease. Further, it is known that when an ocular surface receives a grave disorder due to some causes, apoptosis occurs on the ocular surface. For example, it is reported that apoptosis play a role in interstitial keratitis due to herpes simplex and corneal cell death after irradiation of ultraviolet (Klin Monatsbl Augenheilkd Vol. 217 No. 3: 178-182, 2000, Cornea Vol. 19 No. 1: 99-103, 2000, the cited references are herein incorporated by reference).
Accordingly, development of a new apoptosis controlling agent (i.e., apoptosis inhibitor or apoptosis inducer) which may provide a new type of drug with novel mode of action and be useful in a variety of fields including immune system, cerebral nerve system, optic nerve system, cancer and aging are desired.
Apoptosis can be induced by various kinds of stimulants including biological factors and ultraviolet irradiation. Despite of the stimulant, apoptosis process commonly includes cascade type activation of a group of proteolytic enzymes called as caspase family, which present in the cells. Namely, cell death inducing factor activates the cascade to activate caspases, especially caspase-3, and caspase-3 activates endonuclease fragmentizing DNA to cause apoptosis. Accordingly, the caspase activity, especially the caspase-3 activity can be used as an effective index of apoptosis.
Substances known to inhibit apoptosis include inhibitor of interleukin 1 converting enzyme, basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) (Japanese Patent Application Laid Open No. HEI.10-194988, the cited reference is herein incorporated by reference). Isocarbacyclin derivative has an inhibitory action on apoptosis of nerve cells and the like (U.S. Pat. No. 6,087,395, the cited reference is herein incorporated by reference), and prostaglandin E1 has an inhibitory action on daunorubicin-induced apoptosis of human leukemia cells (Japanese Journal of Inflammation Vol. 18, No. 5: 369-376, 1998, the cited reference is herein incorporated by reference).
Albumin is a protein that is widely present in animal/vegetable tissues and body fluids such as serum and lacrimal fluid. For example, human serum albumin is used for treating hypoalbuminemia, hemorrahagic shock and the like. In the ophthalmic field, it is also known to use albumin as a stabilizer in protein formulations such as fibronectin and interferon. The present inventor has previously proposed to use albumin for treatment of keratoconjuctival disorders or dry eye (U.S. Pat. No. 6,043,213, the cited reference is herein incorporated by reference). However, it is not known that albumin has an apoptosis inhibitory action.